CN101756907A - Oral solid preparation containing polyene phosphatidyl choline and preparation method thereof - Google Patents
Oral solid preparation containing polyene phosphatidyl choline and preparation method thereof Download PDFInfo
- Publication number
- CN101756907A CN101756907A CN200910079858A CN200910079858A CN101756907A CN 101756907 A CN101756907 A CN 101756907A CN 200910079858 A CN200910079858 A CN 200910079858A CN 200910079858 A CN200910079858 A CN 200910079858A CN 101756907 A CN101756907 A CN 101756907A
- Authority
- CN
- China
- Prior art keywords
- polyene phosphatidylcholine
- preparation
- oral solid
- solid formulation
- antioxidant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to an oral solid preparation containing polyene phosphatidyl choline and a preparation method thereof. The oral solid preparation comprises polyene phosphatidyl choline as a raw material, antioxidants and related accessories necessary for corresponding forming of the preparation. The procedure is as follows: cryogenically comminuting and sieving the polyene phosphatidyl choline, and then pelletizing, granulating and drying under reduced pressure; then adding accessories for the corresponding preparation, thereby obtaining the corresponding oral solid preparation according to the procedure for corresponding forming of the preparation. The finished preparation is convenient for clinical using and has good material liquidity for production and preparation, which leads to an easy operated forming process of corresponding preparation formation with good quality control.
Description
Technical field
The present invention relates to the polyene phosphatidylcholine is the oral solid formulation (comprising tablet, capsule, granule, drop pill, soft capsule etc.) of primary raw material, and especially a kind of flowability better contains granulate material of polyene phosphatidylcholine and preparation method thereof.
Background technology
Polyene phosphatidylcholine is a soybean extract---the further extract of soybean phospholipid, and consistent with important endogenous phospholipid on chemical constitution.
Modern pharmacological research shows that polyene phosphatidylcholine enough reduces hepatocellular fatty infiltration; Reduce inflammatory reaction; Promote liver cell regeneration by increasing RNA and proteinic synthesizing with glycogen content; By suppressing collagenation, reducing collagen/DNA ratio and the formation of liver hydroxyproline generation reduction connective tissue; Polyene phosphatidylcholine can be protected sinusoidal endothelial cell regulating liver-QI cell biological film to avoid damage, repair membrane damage, promote film regeneration.This product can make the liver plasma membrane tissue regeneration, coordinates the function between phospholipid and the cell membrane tissue, thereby can make lipid metabolism, synthetic protein and the function of detoxification etc. of liver recover normal effectively.This product has good lipotropy; its effective ingredient structure and cell membrane phospholipid are basic identical, and contain a large amount of unsaturated fatty acids, and energy the liver protecting cellularity reaches has dependent enzyme system to phospholipid; prevent hepatic necrosis and new connective tissue hypertrophy, promote hepatopathy rehabilitation.Generally accepted and extensively employing by clinical.Be applicable to various types of hepatopathys, as: hepatitis, chronic hepatitis, hepatic necrosis, liver cirrhosis, hepatic coma (comprising forerunner's hepatic coma), fatty liver (also seeing the diabetes patient), cholestasis, poisoning, the recurrence of prevention cholelithiasis, perioperative treatment (especially hepatobiliary surgery), gestosis (comprising vomiting), psoriasis, neurodermatitis and radiation syndrome.
Because polyene phosphatidylcholine is originally as a kind of amphiphatic molecule, room temperature is semi-solid state down, and the pure product of polyene phosphatidylcholine are white cured shape solid, and are crystallizable under the low temperature, are insoluble to acetone, ethyl acetate.Dissolve in methanol, ethanol, EC.Polyene phosphatidylcholine is exposed to easily oxidation in the air, color and luster deepens brown, easy oxidation scission of link under its high temperature, acidity, the illumination condition, therefore making of mobile better material is the research emphasis of oral solid formulation preparation, here selecting with polyene phosphatidylcholine compatibility relevant auxiliary materials good and that safety is good is the key of prescription composition, and the appropriate process technology is shaped preparation and the key that is easy to produce work.
Because phospholipid material semisolid characteristics, promptly fusion is in a liquid state, is thick or semi-solid state under the room temperature more than 60 ℃, and make and to limit the development difficulty that has strengthened the oral solid formulation kind because of corresponding production equipment, and then can not provide how suitable dosage form and manufacturer to select for the medication of clinical this series products, and the price of existing manufacturer medicine is also expensive, is unfavorable for the universal utilization on such clinical drug.
At present, domestic commercially available relevant solid preparation has only capsule a kind of, and its preparation generally is that the phospholipid raw material is made by adopting " fusion-fill-cooling technology ".This technology production controllability is difficult to hold, and yield rate is also lower, thereby manufacturing cost is higher; Need special installation production; Quality controllability difference and finished product loading amount detection accuracy are bad in the production process, are difficult to ensure drug quality.
In sum; find a kind of more suitable flowability to contain polyene phosphatidylcholine granulate material and preparation method thereof preferably; large-scale production and quality to the phospholipid oral solid formulation are accurately controlled of crucial importance; to guaranteeing that clinical abundant safe handling medicine also is very necessary, the treatment cost that reduces the patient also there is certain promotion meaning.
At the solution of polyene phosphatidylcholine oral solid formulation processing difficulties, the domestic related application that several pieces of distinct methods are arranged.All the seeing of at present relevant patent situation retrieval, application number: 200610104366.9, the invention compositions is made up of polyene phosphatidylcholine, vitamin, cosolvent, antioxidant; Application number: 200710100460.1, compositions contains polyene phosphatidylcholine, makes corresponding preparations by common methods.
In a word, show, there is no the identical content report of the present invention through relevant patent and prior art literature search result.
Summary of the invention
The objective of the invention is to overcome the deficiency of unfavorable rerum natura of polyene phosphatidylcholine raw material and existing preparation technique; improve the flowability of phospholipid material; so that help the process scaleization and the universalness production preparation of its relevant oral solid formulation; select for the use of this class medicine clinically provides safer, how suitable oral solid formulation, be that a kind of production operability is stronger, quality controllability better, improved the corresponding preparations preparation method of finished product working modulus and safety and effectiveness.In addition, the adding of antioxidant, the stability that can improve the quality of products.
The present invention is achieved by the following technical solutions.Component of the present invention and percentage by weight thereof are: the polyene phosphatidylcholine oral solid formulation, each component and weight percentage ranges thereof that it comprises are: polyene phosphatidylcholine 1～20%, antioxidant 0.1～3%, necessary relevant auxiliary materials is an amount of when reaching the corresponding preparations molding.
Preferably polyene phosphatidylcholine 5～15%, antioxidant 0.1～2%, and necessary relevant auxiliary materials is an amount of when reaching the corresponding preparations molding.
More preferably polyene phosphatidylcholine 10%, antioxidant 1%, and necessary relevant auxiliary materials is an amount of when reaching the corresponding preparations molding.
Indication oral formulations of the present invention comprises tablet (comprising lamellar dosage forms such as sheet, dispersible tablet, sublingual lozenge, chewable tablet), capsule, granule, soft gelatin capsule, drop pill, soft capsule etc.That indication mouth tablet, capsule, granule also comprise is slow, controlled release agent and enteric agents.The indication antioxidant comprises folic acid, vitamin C etc., excellent finger folic acid.
Preparation method of the present invention is: polyene phosphatidylcholine carried out pulverize at low temperature, sieves, get the recipe quantity polyene phosphatidylcholine, add antioxidant, and the following granulation of nitrogen then, granulate, drying under reduced pressure forms flowability material system preferably.Afterwards, the moulding process through corresponding preparations promptly gets corresponding oral solid formulation.
The Lowtemperaturepulverizer temperature is controlled at below-0 ℃ in the above-mentioned preparation method, and more preferably temperature is controlled at-30 ℃～-100 ℃.
Between 30 ℃～15 ℃ of the granule drying under reduced pressure temperature, pressure is 0.01～0.09MPa, is preferably 15 ℃～20 ℃ in the above-mentioned preparation method, and pressure is 0.01MPa.
The present invention has following advantage: the present invention adopts freeze grinding technology earlier the polyene phosphatidylcholine raw material to be carried out relevant treatment, adopt suitable granulation technique to make the good granular pattern system of material fluidity then, make material form and be easier to produce under common solid preparation equipment and the working condition corresponding all kinds of solid preparation, and the yield rate and the quality accuracy of related preparations have been improved, be more conducive to the quantitatively control and the detection of finished product loading amount of centre of product quality simultaneously, thereby the safety and effectiveness of product and quality stability are better.
The specific embodiment
Embodiment 1 (A)
Dosage form: drop pill, specification 76mg/ grain (in polyene phosphatidylcholine)
Polyene phosphatidylcholine is placed Lowtemperaturepulverizer, be crushed to 100 orders under-60 ℃～-70 ℃ temperature, sieve; Get polyene phosphatidylcholine 326g, folic acid 33g, the following granulation of nitrogen then, granulate, 15 ℃, drying under reduced pressure under the 0.01MPa; Get dry thing and join in the fused 977g stearic acid, be stirred to mix homogeneously fast, drip system, ball is washed in cooling, promptly gets 3000 drop pill, and every drop pill content nearly weighs 0.45g.
Embodiment 2 (B)
Dosage form: capsule, specification: 57mg/ grain (in polyene phosphatidylcholine)
Polyene phosphatidylcholine is placed Lowtemperaturepulverizer, be crushed to 100 orders under-40 ℃～-50 ℃ temperature, sieve; Get polyene phosphatidylcholine 326g and vitamin C 33g mixing, again with starch 1629g, microcrystalline Cellulose 1303g, increase progressively mixing by equivalent, detect intermediate content, measure bulk density, encapsulated or the dress enteric coated capsule, make 4000 altogether, every capsules content nearly weighs 0.8g.
Embodiment 3 (C)
Dosage form: tablet, specification: 76mg/ grain (in polyene phosphatidylcholine)
Polyene phosphatidylcholine is placed Lowtemperaturepulverizer, be crushed to 100 orders under-70～-80 ℃ of temperature, sieve; Get polyene phosphatidylcholine 326g, folic acid 33g mixing, again with pre-gel starch 977g and carboxymethyl starch sodium 326g, by equivalent incremental method mixing, granulation, granulate, 20 ℃, 0.08MPa drying under reduced pressure 3 hours, tabletting, the bag film-coat makes 3000 altogether.Every nearly weighs 0.56g.
Embodiment 4 (D)
Dosage form: granule, specification: 76mg/ grain (in polyene phosphatidylcholine)
Polyene phosphatidylcholine is placed Lowtemperaturepulverizer, be crushed to 100 orders under-70 ℃～-80 ℃ temperature, sieve; Get polyene phosphatidylcholine 196g, folic acid 33g, pre-gel starch 977g, carboxymethyl starch sodium 326g, nitrogen is granulated down, granulate, and 15 ℃, 0.02MPa drying under reduced pressure 4 hours is made the 1000g granule altogether.
Embodiment 5 (E)
Dosage form: soft capsule, specification: 228mg/ grain (in polyene phosphatidylcholine)
With gelatin: glycerol: water (1: (0.3～0.4): (0.7～1.4)) mix homogeneously, make offset plate; Polyene phosphatidylcholine is placed Lowtemperaturepulverizer, be crushed to 100 orders under-70 ℃～-80 ℃ temperature, sieve; After getting polyene phosphatidylcholine 326g and folic acid 33g mixing, place between the offset plate, promptly with the punching block compacting.
Embodiment 6
Finished product is tested
Assay is mainly polyene phosphatidylcholine PC, and related substance (related meanings resolve see " Chinese pharmacopoeia) is hemolytic phospholipid LPC, and the leading indicator testing result sees Table.
The tablet finished product detection of table 1 embodiment 3 is table as a result
Table 2 embodiment 2 capsule finished product detection are table as a result
Table 3 embodiment 1 drop pill finished product detection is table as a result
Table 4 embodiment 4 granule finished product detection are table as a result
Table 5 embodiment 5 soft capsule finished product detection are table as a result
Conclusion: relevant leading indicator testing result conformance with standard regulation.
Claims (8)
1. the oral solid formulation that contains polyene phosphatidylcholine is characterized in that component and percentage by weight thereof are: polyene phosphatidylcholine 1～20%, and antioxidant 0.1～3%, necessary relevant auxiliary materials is an amount of when reaching the corresponding preparations molding.
2. according to the described oral solid formulation that contains polyene phosphatidylcholine of claim 1, it is characterized in that component and percentage by weight thereof: polyene phosphatidylcholine 5-15%, antioxidant 0.1-2%, necessary relevant auxiliary materials is an amount of when reaching the corresponding preparations molding.
3. according to the described oral solid formulation that contains polyene phosphatidylcholine of claim 1, it is characterized in that component and percentage by weight thereof: polyene phosphatidylcholine 10%, antioxidant 1%, necessary relevant auxiliary materials is an amount of when reaching the corresponding preparations molding.
4. the oral solid formulation that contains polyene phosphatidylcholine according to claim 1 is characterized in that the indication antioxidant comprises folic acid, vitamin C etc., excellent finger folic acid.
5. the preparation method that contains the oral solid formulation of polyene phosphatidylcholine is: with the polyene phosphatidylcholine of recipe quantity elder generation pulverize at low temperature, mix, sieve, add antioxidant, the following granulation of nitrogen then, granulate, drying under reduced pressure forms flowability granulate material system preferably; Pass through the moulding process of corresponding preparations again, promptly get corresponding oral solid formulation.
6. the preparation method that contains the oral solid formulation of polyene phosphatidylcholine according to claim 5 is characterized in that, below the pulverize at low temperature operative temperature-0 ℃, is preferably-30 ℃～-100 ℃; Between 30 ℃～15 ℃ of the granule drying under reduced pressure temperature, pressure is 0.01～0.09MPa, is preferably 15 ℃～20 ℃, and pressure is 0.01MPa.
7. the described polyene phosphatidylcholine oral solid formulation that contains of claim 1 to 6 is characterized in that the indication oral formulations comprises tablet, capsule, granule, soft gelatin capsule, drop pill, soft capsule etc.
8. the polyene phosphatidylcholine oral solid formulation preparation method that contains according to claim 7 is characterized in that, that indication oral tablet, capsule, granule also comprise is slow, controlled release form and enteric dosage form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100798580A CN101756907B (en) | 2009-03-13 | 2009-03-13 | Preparation method of oral solid preparation containing polyene phosphatidyl choline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100798580A CN101756907B (en) | 2009-03-13 | 2009-03-13 | Preparation method of oral solid preparation containing polyene phosphatidyl choline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101756907A true CN101756907A (en) | 2010-06-30 |
| CN101756907B CN101756907B (en) | 2011-08-31 |
Family
ID=42488393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100798580A Expired - Fee Related CN101756907B (en) | 2009-03-13 | 2009-03-13 | Preparation method of oral solid preparation containing polyene phosphatidyl choline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101756907B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103251568A (en) * | 2013-05-06 | 2013-08-21 | 合肥博思科创医药科技有限公司 | Oral solid preparation containing polyene phosphatidyl choline and preparation method thereof |
| CN103908440A (en) * | 2013-01-09 | 2014-07-09 | 正大天晴药业集团股份有限公司 | Polyene phosphatidylcholine capsule and preparation method thereof |
| CN104000844A (en) * | 2014-06-09 | 2014-08-27 | 山东司邦得制药有限公司 | Granules of iron-based montmorillonite and preparation method thereof |
| CN106606780A (en) * | 2015-10-26 | 2017-05-03 | 深圳澳美制药技术开发有限公司 | Polyene phosphatidyl choline composition, polyene phosphatidyl choline soft capsule and preparation methods |
| CN108272767A (en) * | 2016-12-31 | 2018-07-13 | 湖南斯奇生物制药有限公司 | A kind of pharmaceutical composition containing BCG polysaccharide nucleic acid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100431530C (en) * | 2006-08-10 | 2008-11-12 | 北京国仁堂医药科技发展有限公司 | Soft polyene phosphatidylcholinecapsule and its prepn process |
| CN101045062B (en) * | 2007-02-04 | 2011-07-27 | 杨喜鸿 | Polyenephophatidylcholine enteric coated preparation, its preparing method and application |
-
2009
- 2009-03-13 CN CN2009100798580A patent/CN101756907B/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103908440A (en) * | 2013-01-09 | 2014-07-09 | 正大天晴药业集团股份有限公司 | Polyene phosphatidylcholine capsule and preparation method thereof |
| CN103908440B (en) * | 2013-01-09 | 2016-12-28 | 正大天晴药业集团股份有限公司 | A kind of polyene phosphatidylcholine capsule and preparation method thereof |
| CN103251568A (en) * | 2013-05-06 | 2013-08-21 | 合肥博思科创医药科技有限公司 | Oral solid preparation containing polyene phosphatidyl choline and preparation method thereof |
| CN104000844A (en) * | 2014-06-09 | 2014-08-27 | 山东司邦得制药有限公司 | Granules of iron-based montmorillonite and preparation method thereof |
| CN106606780A (en) * | 2015-10-26 | 2017-05-03 | 深圳澳美制药技术开发有限公司 | Polyene phosphatidyl choline composition, polyene phosphatidyl choline soft capsule and preparation methods |
| CN106606780B (en) * | 2015-10-26 | 2020-05-19 | 深圳澳美制药技术开发有限公司 | Polyene phosphatidyl choline composition, soft capsule and preparation method thereof |
| CN108272767A (en) * | 2016-12-31 | 2018-07-13 | 湖南斯奇生物制药有限公司 | A kind of pharmaceutical composition containing BCG polysaccharide nucleic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101756907B (en) | 2011-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101756907B (en) | Preparation method of oral solid preparation containing polyene phosphatidyl choline | |
| Malviya | Extraction characterization and evaluation of selected mucilage as pharmaceutical excipient | |
| CN101299993A (en) | Carboxyalkylcellulose esters for administration of poorly soluble pharmaceutically active agents | |
| CN102240272B (en) | Potassium citrate sustained release tablet and preparation method thereof | |
| CN101816637B (en) | Leflunomide tablet preparation and preparation method thereof | |
| CN104721142A (en) | Rivaroxaban solid dispersion and preparation method thereof | |
| CN103006594B (en) | A kind of glimepiride composition and method of making the same | |
| RU2012131949A (en) | PHARMACEUTICAL COMPOSITION OF RHEIN OR DIACEREIN AND METHOD FOR PRODUCING IT | |
| CN110123770A (en) | A kind of Eliquis pharmaceutical composition and preparation method thereof | |
| CN107375224B (en) | A kind of Gliclazide sustained-release tablet | |
| CN104414991A (en) | Tranexamic acid solid sustained-release tablets and preparation method thereof | |
| CN111214449B (en) | Cetirizine hydrochloride tablet and preparation method thereof | |
| CN102429912B (en) | Pharmaceutical composition prepared with micronized prasterone or sodium prasterone sulfate and use thereof | |
| CN105055362B (en) | A kind of irbesartan and hydrochlorthiazide piece and preparation method thereof | |
| CN106749174B (en) | A kind of sitafloxacin dihydrate crystal form, preparation method and combinations thereof tablet | |
| CN102824644B (en) | High-stability sustained-release tablet prepared by using hydroxy propyl cellulose | |
| CA2492156C (en) | Tablet composition containing kampo medicinal extract and its manufacturing process | |
| CN101804038A (en) | Huperzine A preparation for treating schizophrenia and nervous function damage and preparation method thereof | |
| CN107028899A (en) | A kind of pharmaceutical composition containing pyridopyrimidines derivatives or its officinal salt | |
| CN103432090B (en) | Cyclovirobuxine D sublingual tablet as well as preparation method and application thereof | |
| CN101829333B (en) | New multi-functional auxiliary material for orally disintegrating tablets and preparation method thereof | |
| CN114099506B (en) | Pharmaceutical composition containing sorafenib | |
| EP4327805A1 (en) | 13c methacetin granule, and preparation method therefor and use thereof | |
| CN111714444B (en) | Ulipristal acetate oral solid preparation and preparation method thereof | |
| CN103142533A (en) | Enteric coated tablet of etoposide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| DD01 | Delivery of document by public notice |
Addressee: Beijing ruiyiren Technology Development Co., Ltd. Document name: Notification of Termination of Patent Right |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110831 Termination date: 20140313 |